Apparatus and method for handling fluids for analysis

Description

BACKGROUND OF THE INVENTION

[0001] The present invention is directed toward a specimen handling device.

[0002] Testing sample biological specimens is commonly done, for example, to check for the presence of an item of interest, which item may be or include all or portions of a specific region of DNA, RNA, or fragments thereof, complements, peptides, polypeptides, enzymes, prions, proteins, messenger RNA, transfer RNA, mitochondrial RNA or DNA, antibodies, antigens, allergens, parts of biological entities such as cells, virons or the like, surface proteins, functional equivalents of the above, etc. Specimens such as a patient's body fluids (e.g., serum, whole blood, urine, swabs, plasma, cerebra-spinal fluid, lymph fluids, tissue solids) can be analyzed using a number of different tests to provide information about a patient's health.

[0003] In such testing, it is imperative that the specimens be handled in a manner which prevents contaminants from being introduced to the specimens, whether from the outside environment or between specimens. For example, where the HIV virus from one specimen is inadvertently allowed to contaminate the specimen of a different patient, the resulting false positive test result could potentially have catastrophic psychological effect on the patient, even should subsequent testing later discover the error. Moreover, since such testing is highly sensitive, even the smallest amounts of contamination can cause erroneous test results. Simply put, it is imperative that the specimens be properly handled.

[0004] In such sophisticated testing, it is also imperative that the various reagents which may be used in the testing be properly handled as well, not only to avoid contaminants but also to ensure that the proper reagent in proper quantities is used at appropriate times.

[0005] Commonly, such testing is accomplished using automated devices which handle multiple specimens and fluids (typically, reagents). Such automated devices typically will use sets of pipettes to move various fluids between their original containers (usually receptacles such as open topped tubes) and containers in which the specimens are to be processed. For example, a set of 8 specimens may be contained in 8 tubes or other receptacles loaded in a rack on the device, and a head carrying 8 pipettes will through programmed motion move the pipettes into those 8 tubes, where a vacuum will be applied to extract a selected amount of each specimen from its tube into the pipettes. The head will then retract the pipettes from the tubes and move over to another set of tubes located at a processing station, depositing the extracted amounts of each specimen from the pipettes into sets of testing tubes.

[0006] At the processing station of such automated devices, the specimens are variously handled according to the purpose of the testing (e.g., incubated, prepared, lysed, eluted, analyzed, read, etc.). For example, the specimens may be prepared for analyzing, as for example by separating DNA or RNA from the specimen. The specimens may also or alternatively be analyzed. Commonly, such processes involve the addition of various fluids (typically reagents) to the specimen in each tube. For example, in a first step, a reagent may be added to each of the tubes to wash the specimens, and second and third (and more) reagents may be added to the specimens in the course of carrying out other processes to, for example, unbind and/or separate the DNA or RNA of interest allow so that it may be extracted from the specimen in each tube for subsequent testing. Similar processes, in which the same or different reagents are added to the tubes, may also occur after the specimen has been prepared as a part of the analyzing of the prepared specimens.

[0007] The handling of the reagents and other fluids can, with such automated devices, be problematic. Though the reagents may be automatically moved from receptacles to the specimen containing tubes in the processing station by use of the head and pipettes such as noted, it is in the first instance necessary to load the appropriate reagent into the appropriate receptacle on the device in order to ensure that the head and pipettes are adding the appropriate reagent to the appropriate specimen containing tube at the appropriate time in the process. Further, it should be recognized that it is necessary for the receptacles to be readily cleaned, whether to remove possible contaminants or to permit use of different fluids in connection with different processes. As a result of such requirements, the receptacles are typically readily removable from the apparatus for such action.

[0008] Heretofore, loading the appropriate reagent into the appropriate receptacle has been accomplished in several different ways. In one such procedure, the individual who is controlling the device manually measures and adds the reagents to receptacles, and then places those receptacles on the device. In another such procedure, the loading of reagents is automatically accomplished by the device itself, which uses some transfer apparatus (such as a head and pipette(s) as previously described) to move the reagents from bulk supplies of the reagents provided with the device.

[0009] However, as already noted, either of the above procedures can be problematic. For example, manually adding the reagents can introduce human error, whether erroneously preparing the reagent, adding reagents to the wrong receptacles, or even mounting the receptacle incorrectly on the device. In the latter case, even if the correct reagents are loaded in the correct amounts, they will be at the wrong location on the device so that when the head and pipettes automatically draw a reagent for use at a certain step of the processing, it may well be the wrong reagent, or there could be no reagent of any kind where the head and pipettes go to extract it. Further, while such errors may be reduced using the second procedure (in which the device itself loads reagents from bulk supplies), the bulk supplies can themselves take up more room than is desirable for the device. Further, allowing this process to be accomplished by the device will, naturally, tie up the device while it carries out those steps. Tying up the device can reduce the amount of tests which are performed during a given day, and thereby either delay the completion of tests or require significant additional investment of capital for additional devices to allow for a desired testing capacity level.

[0010] The present invention is directed to overcoming one or more of the problems as set forth above.

[0011] EP 0 226 867 discloses a pipetting apparatus including a receiving device for test containers, a pickup section for one or more microstandards or Abbott plates, a receiving device for containers for storage of reagents, a feeding device for the pipettes and a pipette hopper, which are situated side by side in a chassis and are accessible from above. The pipetting apparatus contains, in addition, a dosing device situated in a frame movable above chassis, frame being guided in a rail and being moved along rail by a drive unit. The receiving device can accommodate a plurality of test containers, each of which is placed in a support comprising a collet in order to hold the container positionally stable and to enable use of different test containers. Moreover, receiving device includes a drive means for moving test containers relative to dosing device. This drive means comprises twelve drive units disposed in a row and coordinated with each support and an additional drive unit to move the twelve drive units together. In operation, the dosing device pick ups the pipettes situated in slide. Dosing device conveys the pipettes to receiving device of test containers. The test containers are moved in the direction of dosing device until the tips of the pipette pistons come into contact with the liquid. If the levels of the liquid in the test containers are at the same height, the liquid is absorbed by the pipettes. The pipettes are then moved for aspirating the reagents, the distance of the pipettes to the microstandard plate being adapted at the same time, and the pipettes being externally cleansed in cleaning device. Thereafter the liquids absorbed by the pipettes are discharged, for instance, in the microstandard plates.

SUMMARY OF THE INVENTION

[0012] The invention concerns a specimen handling device according to claim 1.

[0013] A preferred embodiment is described by claim 2.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] 

Figure 1 is a perspective partial view of an automated testing device incorporating the present invention;

Figures 2-5 are perspective views of reagent containers and trays used with the testing device of Fig. 1;

Figure 6 is a perspective view of a reagent kit usable with the trays of Figs. 2-5;

Figure 7 is a simplified plan view of the deck of the testing device of Fig. 1;

Figure 8 is a simplified cross-sectional view illustrating a cover usable with a processing station of the Fig. 1 testing device in accordance with the present invention;

Figure 9 is a partial view of the deck and trays of an alternative embodiment of an automated testing device incorporating the present invention; and

Figures 10a-10b is a flow chart of a process for using an automated testing device incorporating the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0015] An automated testing device 20 incorporating the invention described herein is illustrated in Fig. 1. For simplicity of explanation of the invention, many of the components of the testing device 20 are not (and need not be) shown in the figures. The automatic testing device may be adapted for the substantial isolation of nucleic acids from biological samples, including the isolation and testing of nucleic acids from biological samples. In that context, Fig. 1 generally illustrates a deck 22 of the testing device 20 on which testing of specimen samples may be done. In the testing device 20 as discussed herein, specimens may be loaded onto the deck 22 of the device 20 along with other items necessary for the desired test, such as reagents and pipettes. A hood 26 is also generally shown in Fig. 1 to protect against contamination from the environment in which the device 20 is located. The hood 26 may be any suitable enclosure for preventing outside contaminants from entering therein as is known in the art, and the particular hood 26 used is not significant to the present invention except insofar as it may be opened to allow the device operator access to the deck 22 as is common. Although not shown, the automatic testing device may advantageously also include one or more of the following features: (1) two heating elements, each capable of controllably heating volumes of up to 168 milliliters (48 tubes x 3.5 milliliters per tube) to at least 50°C and more preferably at least 75°C, (2) a receptacle to hold and segregate from samples and reagents used pipette tips such that contamination from used tips is minimized, (3) aerosol control devices, for example without limitation, (a) a sample tube or reagent tube sealer, (b) electrodes for treating surfaces and/or liquids with electrical current capable of modifying nucleic acids, (c) an ultraviolet light source capable of degrading or modifying nucleic acids, (d) an apparatus for causing laminar air flow in or around the automatic testing device, (4) a temperature controller capable of cycling temperatures of samples and/or reagents in a manner suitable for PCR, (5) magnets for use in combination with a pipettor or other aspiration system capable of substantially separating magnetic particles from liquids in which they may be suspended, and (6) an optical detector (e.g., a flourometer) for measuring the light absorbance or fluorescence of processed samples.

[0016] Inside the hood 26 and disposed above the deck 22 is a head 30 including a linear array of pipettors 32 suitably adapted to releasably secure disposable pipettes thereto as is known. The array of pipettors 32 is arranged in a selected uniform spacing for purposes which will become apparent. Moreover, the head 30 may suitably support the pipettors 32 so that the uniform spacing therebetween may be selectively adjusted. A suitable drive and controller is provided with the device 20 to control movement of the head 30 and pipettors 32.

[0017] Suitable racks 34 are provided for supporting tubes 36 with specimens therein, with the racks 34 being removably secured to the deck 22 such as further detailed hereafter.

[0018] A processing station 40 is located on the deck 22, at which specimen samples may be processed. In the present description, the processing is to isolate an analyte of interest from the specimen (e.g., DNA or RNA), after which processing the isolated analyte may be further tested according to an appropriate protocol. However, it should be understood that the present invention is not limited in any way to such processing, and could as easily be used with a device in which different processing or protocols are carried out.

[0019] In the disclosed embodiment, the processing station 40 includes four stations 40a-d, where samples of the specimens from the tubes 36 in the racks 34 may be processed according to testing requirements. Test tubes or reaction vessels 42 in a support bracket 44 may be suitably moved between the stations 40a-d, for example by transfer arms 46 suitably controlled and driven to pick up and move the support bracket in the hood 26 as desired. For example, while the bracket 44 is shown at station 40b in Fig. 1, during the initiation of the processing, the bracket 44 may be at station 40a, where specimen samples are initially loaded into supported test tubes 42. As described in more detail below, some processing may occur at station 40a, such as washing the specimen samples, after which the transfer arms 46 move the support bracket 44 to a second station 40b, where different processing (e.g., lysis) may occur. Different conditions may be provided at different stations 40a-d (e.g., heating, cooling, magnetic fields) according to the protocols for the processing being done. As also described in more detail hereafter, different reagents may be introduced to the test tubes 42 at each station.

[0020] While different reagents may be used within the scope of the invention (with the reagents being principally dependent on the desired processing of the specimen samples), where the processing is sample preparation in which a particular biological item of interest is to be analyzed, the reagent may advantageously include particles having an affinity for those biological analytes of interest. Particles having affinity for biological analytes of interest that are useful in the context of the present invention include, without limitation, particles having glass, silica or metal oxide surfaces. Similarly, the automatic testing device may be constructed so as to resist the corrosive effects of strong bases (e.g., potassium hydroxide) and reagents comprising high concentrations of chaotropes commonly used in the isolation of nucleic acids (e.g. 4.5 M (or higher) guanidinium isothiocyanate or 5 M (or higher) urea.

[0021] A plurality of trays 50a-d having receptacles 52 for different reagents are also provided, with the trays 50a-d being removably secured to the deck 22 such as further detailed hereafter. Further, a pipette supply station 60 is also secured to the deck 22, with the pipette supply station 60 being loaded with supplies of different sized and disposable pipettes 62 for use by the device 20.

[0022] Racks 66 supporting tubes 68 for processed specimen samples are also removably securable to the deck 22. In the illustrated embodiment, for example, DNA isolated at the processing station 40 may be removed from the test tubes 42 and transferred by the head 30, pipettors 32 and suitable pipettes 62 to the tubes 68 in racks 66. Further processing of the isolated DNA may then be separately done according to protocol appropriate for analyzing, for example, a specific region of the DNA. Additional equipment may be included in the device 20 if necessary for such protocol. Again, it should be noted that the present invention may be used with virtually any type of processing, in particular where different fluids such as reagents are used in the processing. The racks 66 may be releasably secured to the deck 22 to allow washing and decontamination of the racks 66.

[0023] Figs. 2-5 illustrate the four trays 50a-d together with pre-mixed and measured containers or packages 70, 72, 74, 76, 78. The containers 70-78 are provided in a kit 80 (see Fig. 6) which contain five different containers 70-78 all for use in processing a specific number of specimen samples, with the kit 80 having four groups of those containers 70-78.

[0024] The kit 80 may be packaged in any suitable manner, including that illustrated in Fig. 6 in which a single box 82 is provided with two boxes 84, 86 therein, with each interior box 84, 86 including a divider 88 therein separating two different groups of containers 70-78. The kit can optionally also contain instructions relating to the use of the kit for the preparation of nucleic acids and/or the use of such prepared nucleic acids in diagnosing a disease or condition.

[0025] In the illustrated embodiment, as an example, it should be appreciated that up to ninety-six specimens may be processed at one time. Thus, the test tubes 36 are arranged in six rows of eight by the support bracket 44, where two different support brackets 44 may be used and shifted between different stations at one time. Similarly, up to four racks 34 may each support twenty-four tubes 36 of specimens in a row, as may up to four racks 66 each support twenty-four tubes 68 for the processed specimen samples. Each of the four groups of containers 70-78 in the kit 80 contain measured amounts of reagents required for processing twenty-four specimen samples. While such numbers of specimens and quantities are convenient (e.g., a head 30 carrying eight pipettes 62 can conveniently move quantities of samples and reagents between such arrays of tubes), it should be understood that the present invention is clearly not limited to a device 20 in which such arrays in such numbers are used.

[0026] Referring again to Figs. 2-5, it can be seen that each tray 50a-d includes open topped receptacles 52a-j which are marked by icons 90, 92, 94, 96, 98 representative of a particular reagent to be used in the processing. For example, icons 94 and 96 may represent a wash fluid. However, the particular graphical representation included in the icon 90-98 can be anything, including numerals or letters or other symbols, colors or combinations thereof, with the important aspect being that the icon used on a particular receptacle 52 match the icon on the container 70-78 containing the reagent to be poured therein.

[0027] Further, the receptacles 52a-j may be marked with an indication of how many reagent containers 70-78 from the kit 80 should be poured into the receptacle depending on the number of specimen samples being processed. For example, it will be understood by the operator that one group of containers 70-78 should be used if 1-24 samples are to be processed, two groups if 25-48 samples are to be processed, three groups if 49-72 samples are to be processed, and all four groups if 73-96 samples are to be processed.

[0028] Where the receptacle 80-88 for a given reagent is adequate in size to hold all of the reagent needed even for full testing (e.g., for ninety-six samples), then the appropriate number of such containers 70-78 should be poured into that receptacle 52a-j depending on the number of samples being tested.

[0029] For reagents which are used in smaller relative quantities, such as the reagents in containers 70 (Fig. 2) and 78 (Fig. 5), all of each reagent may be poured into one receptacle. Thus, when processing a full capacity of ninety-six samples, four containers 70, 78 respectively of those reagents would be poured into the receptacles 52a, 52h marked with the corresponding icon 90, 98. As another example, when processing only 25-48 samples, only two containers 70, 78 of each such reagent would be added to the respective receptacles 52a, 52h.

[0030] Where a larger quantity of a particular reagent is used than can be held by a particular receptacle 52, then multiple receptacles 52b-g, 52i-j are used for that reagent, with a mark provided on the receptacles 52b-g, 52i-j to indicate which to fill based on the number of samples being processed. Thus, for example, referring to Figs. 2-3 where it can be seen that relatively larger quantities of the reagent of container 72 would be used, one container 72 would be poured into receptacle 52b (marked with A1-24") for processing of 1-24 samples, a second container 72 would additionally be poured into receptacle 52c (marked with A25-48", though not seen in the Figure) for processing of 25-48 samples, a third container 72 would additionally be poured into receptacle 52d (marked with A49-72") for processing of 49-72 samples, and a fourth container 72 would additionally be poured into receptacle 52e (marked with A73-96", though not seen in the Figure) for processing of 73-96 samples. Such a marking thus helps to ensure that appropriate reagent is used when less than 73 (in the present example) samples are being processed (e.g., the head 30 will be controlled to go to only receptacles 52b-d for 72 samples, and an error would occur if one of the three containers 72 with that reagent were poured into receptacle 52e, leaving one of receptacles 52b-d empty).

[0031] Similarly, for reagents used in intermediate amounts (such as in containers 74 and 76), two receptacles (52f-g and 52i-j, respectively) may be used, with the first two containers (74 or 76) of a particular reagent being poured into a first receptacle marked with A1-48" (52f or 52i, respectively), and additional containers of that reagent poured into a second receptacle (52g or 52j, respectively) marked A49-96" where more than 48 samples are being processed. Alternate methods of pouring quantities of a particular reagent into multiple receptacles would, however, be possible.

[0032] It can thus be appreciated that through the use of the kit 80 and trays 50a-d with receptacles 52a-j and icons 90-98, an individual operator of the device 20 may readily and reliably provide the proper amount and mixture of reagents for use by the machine, with minimal risk of operator error in doing so. Further, this operation may also be accomplished without requiring that the device itself be programmed to do so, be tied up in doing so, or be required to hold bulk quantities in doing so. Further, the use of such prepared reagents in specific containers 70-78 readily allows for a preselected quantity of internal control particles to be precisely and reliably added to the reagents to advantageously allow for a later estimation of how efficiently the analyte of interest (e.g., DNA) is isolated by the processing. Such internal control particles may be easily measured in a known specific quantity for use with the known standard quantity of reagent in the particular container 70-78, so that an appropriate fluid mix may be provided for the desired sample processing.

[0033] As also shown in Figs. 2-5, in addition to the use of icons 90-98 to ensure that the proper quantities of the proper reagents are used for processing, a second set of icons 100, 102, 104, 106 are also used on the end of the trays 50a-d in conjunction with matching icons 100-106 on the deck 22 to ensure that the operator can easily and reliably locate each tray 50a-d at the proper location on the deck 22. These icons 100-106, too, can be anything, including numerals or letters or other symbols, colors or combinations thereof. This use of these icons 100-106 thus further ensures that the trays 50a-d and receptacles 52a-j are properly positioned on the deck 22, so that the head 30 will pick up the proper reagents when it proceeds according to its programmed operation to a particular location at which the receptacle for that reagent is supposed to be located.

[0034] Reference will now be had to Fig. 7 to generally explain an operation in which 96 samples are to be processed. While the head 30 is not shown in this view, it should be understood that it will travel over the components illustrated and lower pipettes 62 into tubes 36, 42, 68 and receptacles 52a-j to pick up fluids (i.e., specimen samples and reagents) and then move over the deck 22 to a different location over different tubes 42, 68 into which the picked up fluid is discharged.

[0035] For example, the head 30 would initially move over the pipette supply station 60 to pick up a set of eight pipettes 62 of the appropriate size, and then move to the first row 120 of specimen tubes to pick up eight specimen samples (e.g., from the last eight tubes [those in the top of Fig. 7] in row 120), and then move to the eight test tubes 42 located in row 140a at station 40a, where it discharges those specimen samples. Typically, some (e.g. six) of the first eight specimen samples would contain known materials so that the results of the analysis when processing is completed can be checked for accuracy.

[0036] The head 30 would then move over a discharge chute 146, where it would drop off the contaminated pipettes 62 (with the chute 146 open to a trash receptacle beneath the deck 22), and then proceed to the pipette supply station 60 for new pipettes 62, which it would then use to pick up eight specimen samples (e.g., from the other eight tubes in row 120) for transfer to the eight test tubes 42 located in row 140b at station 40a. This process would repeat for each set of eight specimens until all ninety-six test tubes 42 (in six rows 120, 122, 124, 126, 128, 130) have been provided with specimen samples.

[0037] At this point, the head 30 would be used to pick up an appropriate reagent from the appropriate receptacle 52a-j as required for the first step of processing, and then discharge that reagent into each of the various test tubes 42. With a head 30 having eight pipettes 62, such a process could involve up to twelve steps in picking up the first reagent.

[0038] Thereafter appropriate processing occurs at the processing station 40. This could involve, for example, using the transfer arms 46 to move the support brackets 44 between the different stations 40a-d for different steps of the process, with additional different reagents added at those different steps from the various receptacles 52a-j. At the completion of this processing, the item of interest (e.g., the isolated DNA) would be transferred by use of the head 30 and pipettes 62 to tubes 68 in trays 66 in rows (150, 152, 154, 156, 158, 160) which correspond to the tubes 36 in rows 120-130 which initially held the specimens.

[0039] As with the trays 50a-d for the receptacles 52a-j, the racks 34, 66 for the specimens may also be advantageously provided with icons thereon matching icons on the deck 22 to ensure that the racks 34, 66 are properly located on the deck 22. This enables the operator to reliably match the processed specimen sample in the tubes 68 in racks 66 with the specimens in the tubes 36 in the racks 34 and, in essence, allows the operator to reliably tell which processed sample is related to which specimen.

[0040] It should also be noted that in the above operation, the movement of the head 30 is advantageously controlled so that it moves the pipettes 62 over and between the various tubes 36, 42 to minimize the possibility of contamination of specimen samples. That is, by supporting the pipettes 62 on the head 30 with a selected spacing matching that of the tube rows, the head 30 is controlled to move so that when the pipettes 62 pass over a row of tubes 36, 42, they will be between the tubes 36, 42 as they do so. Moreover, with the pipettor spacing adjustable as previously noted, such an advantage may be obtained while at the same time allowing compact presentation of various components. For example, as can be seen in Fig. 7, the receptacles 52a-j and pipette supply station 60 can be arranged in significantly shorter row lengths than can the test tubes 42, thereby allowing each component to be provided so as to take up minimal space on the deck 22 notwithstanding relatively large space requirements for other components. For example, a test tube 42 can require more space than a stack of pipettes not only because it is relatively larger but also because processing on the deck 22 can require certain spacing between the tubes 42 which is not required for other components (e.g., reliably uniform heating of all tubes in a tube array may require that suitable heat sources [and space for those heat sources] be provided throughout a tube array, and sample processing components, such as magnets, may similarly need to be dispersed through a tube array). The spacing of the pipettors 32 may thus be advantageously adjusted to different uniform amounts, depending upon the component over which it is passing, to permit the supported pipettes to pass over and between the components, whatever the uniform spacing of the components, and thereby minimize the risk of contamination.

[0041] Fig. 8 illustrates an alternative embodiment which may be used in conjunction with, the above described operation in which the pipettes 62 are moved between tubes 36, 42 as they pass thereover to prevent contamination. Specifically, an overlapping cover 170 may be provided above the tubes in the processing station 40, where the panels 172, 174, 176 of the cover 170 may be moved in the direction of the arrows to overlapping positions to uncover a particular row of tubes 42 into which the pipettes 62 are to discharge a fluid (sample or reagent), while keeping the remaining tubes 42 covered and thereby protected from possible contamination.

[0042] Fig. 9 illustrates yet another alternative embodiment which may be used in conjunction with, the above described structure using icons 100-106 to ensure proper placement of the trays 50a-d on the deck 22. In this alternative, the deck 22 is provided with uniquely shaped pins 180a-d projecting therefrom at each location at which the trays 50a-d are to be positioned. The trays 50a-d are also provided with matching shaped slots 182a-d in the bottoms thereof whereby each tray 50a-d can only be secured at one position on the deck 22.

[0043] Still further, as also illustrated in Fig. 9, each tray 50a-d may also be provided with a suitable machine readable indicator 186a-d (such as a bar code) unique to each tray 50a-d, with a suitable reader 188 provided with the device 20, where the reader 188 scans the indicators 186a-d to verify proper positioning. The verification of the reader 188 could either be used to alert the operator to an error in loading the trays 50a-d, or could be used to adjust the controller for the head 30 to ensure that the head 30 goes to the proper receptacles 52a-j at the proper time during processing. It should be understood that while the above description of Fig. 9 has been made in reference to the trays 50a-d having the reagent receptacles 52a-j, the same structure could also be used to ensure proper positioning of the specimen and processed sample racks 34, 66.

[0044] Figs. 10a-10b illustrate the process of operating the device 20 such as previously described, but using a bar code reader 188 such as illustrated in Fig. 9. Prior to the start 200, the operator has already poured the various reagents from the containers 70-78 of the kit 80 into the various receptacles 52a-j, according to the number of specimen samples being processed, and reagent trays 50a-d and specimen and processed sample racks 34, 66 have been positioned on the deck 22 along with a suitable supply of pipettes.

[0045] After the operator suitably indicates to the device 20 that it may begin, the reader 188 at 202 reads the indicators 186a-d (e.g., bar codes) on the trays 50a-d (and racks 34, 66). If it detects at 204 that the trays 50a-d (and racks 34, 66) are not properly positioned, it sends an error message at 206 to the operator and stops operation 208 until the operator repositions the trays and racks to the proper position and starts again. If it detects at 204 that everything is positioned properly, operation continues with the head 30 moving at 210 to pick up eight pipettes 62, with the pipettes then moved at 212 to pick up a reagent from an appropriate receptacle 52a-j. The picked up reagent is then delivered at 214 to the test tubes 42.

[0046] The pipettes 62 may be discarded at 216 after only one use if contamination is a concern at that point, in which case steps 210-216 are repeated as necessary, as indicated at 218, until the first reagent has been loaded into all of the test tubes 42 which will receive specimen samples to be processed. Alternatively, if the reagent is to be added to more than eight test tubes 42 (e.g., to forty eight test tubes 42) where contamination with other materials is not a concern during that step, step 210 may be skipped and steps 212-216 repeated until it is determined that new the pipettes can/should be discarded, such as may occur when the first reagent has been added to all of the tubes 42 to be processed (e.g., six times for forty eight test tubes 42).

[0047] Once the first reagent has been loaded into all of the test tubes 42, steps 210-216 may further be repeated (as also indicated at 218) to add additional reagents to the test tubes 42 as desired. For example, uParticles may first be added to the tubes 42, and then Lysis buffer may be added. Of course, the reagents used may vary depending on the processing desired, and the present invention is not limited to use of any particular reagents.

[0048] If samples are to be added, as determined at 219, a similar process is then repeated at 220-228 wherein the samples are moved from eight sample containing tubes 36 to eight of the test tubes 42 for the first step of processing the samples, with those steps repeated at 228 until all of the specimen samples to be tested have been placed in test tubes 42. While the pipettes used to deliver specimen samples typically are required to be discarded after each use as at 226 to prevent contamination, it would be within the scope of the present invention to reuse pipettes if contamination does not necessitate using new pipettes (such as might occur, e.g., if additional quantities of the same specimen samples are to be delivered to the tubes 42 in more than one step).

[0049] If additional reagents are required after the specimen samples have been delivered to the test tubes 42 as determined at 230, operation returns to picking up pipettes at 210 for repetition of steps 210-218 as necessary. Once sufficient reagents have been added, operation then skips at 219 (since the samples have already been added at steps 220-228 and thus do not need to be added) to step 234 to determine whether processing should occur.

[0050] If sample processing is then ready to be done at 234, sample processing proceeds at 236. Any variety of process steps may be done at this stage, including washing, incubating and lysing, although again it should be understood that the present invention may be advantageously used irrespective of the particular processing being done on the samples.

[0051] If further sample processing is required at 238 using additional reagents, steps 210-236 are repeated to add those reagents and process the samples.

[0052] Once sample processing is completed as determined at 234, at 240 the pipettes 62 are used to deliver the processed samples to the tubes 68 in the racks 68, at which point (at 242) this phase of processing ends.

[0053] By adding the reagents to the test tubes 42 before the samples such as described in the above operation, the risk of contamination between samples may be minimized. The present invention could also be advantageously used with, for example, a different order of adding reagents and samples (e.g., the samples could be added to the test tubes 42 before adding the reagents).

[0054] It should now be apparent from the above that the present invention may be used to ensure that samples and reagents may be processed without serious risk of contamination of the samples.

[0055] Still other aspects, objects, and advantages of the present invention can be obtained from a study of the specification, the drawings, and the appended claims.

[0056] Where technical features mentioned in any claim are followed by reference signs, those reference signs have been included for the sole purpose of increasing the intelligibility of the claims and accordingly, such reference signs do not have any limiting effect on the interpretation of each element identified by way of example by such reference signs.

Claims

1. A specimen handling device, including:

a deck (22) having a plurality of positions defined thereon, including a plurality of open top receptacles (52) each adapted to contain a reagent therein;

a head (30) adapted to carry selected fluids in X pipettes (62) over said deck (22), X being 3 or more;

a drive and controller controlling movement of said head (30) to pick up pipettes (62) arranged in a row with uniform spacing therebetween;

characterised in that said handling device further includes racks (34) on said deck (22) for supporting individual open top tubes (36) in groups of X, said racks (34) supporting said tubes (36) in each group with said uniform spacing, said controller being adapted to control movement of said head (30) to move the picked up row of pipettes (62) to one of said open top receptacles (52) to pick up an appropriate reagent through the open top of said one receptacle (52), move the pipettes (62) with picked up reagents from said open top receptacles (52) to a selected group of said tubes (36), said controller being adapted to move said head (30) over groups of said tubes (36) other than said selected group of said tubes (36) with said pipettes (62) between the tubes (36) when they pass over said other groups of tubes (36).

2. The specimen handling device of claim 1, wherein said uniform spacing between said pipettes (62) carried by said head (30) is adjustable, and said controller further controls said head (30) to adjust said spacing between said pipettes (62) to match the uniform spacing of the racks (34) over which said pipettes (62) pass.

Ansprüche

1. Eine Proben-Handhabungsvorrichtung, die Folgendes einschließt:

ein Deck (22) mit einer Vielzahl darauf definierter Positionen, einschließlich einer Vielzahl von Behältern (52) mit offener Oberseite, von denen jeder ausgebildet ist, um ein Reagenz darin zu enthalten,

einen Kopf (30), der ausgebildet ist, um ausgewählte Flüssigkeiten in X Pipetten (62) über das Deck (22) zu tragen, wobei X 3 oder mehr bedeutet,

einen Antrieb und eine Steuerung, die Bewegung des Knopfs (30) zur Aufnahme der Pipetten (62) steuernd, die in einer Reihe mit gleichmäßigem Abstand dazwischen angeordnet sind,

dadurch gekennzeichnet, dass die Handhabungsvorrichtung weiter Gestelle (34) auf dem Deck (22) zum Tragen einzelner Röhrchen (36) mit offener Oberseite in Gruppen von X einschließt, wobei die Gestelle (34) die Röhrchen (36) in jeder Gruppe mit dem gleichmäßigen Abstand tragen, wobei die Steuerung ausgebildet ist, um die Bewegung des Knopfes (30) zu steuern, zum Transport der aufgenommenen Reihe von Pipetten (62) zu einem der Behälter (52) mit offener Oberseite, zur Aufnahme eines entsprechenden Reagenz durch die offene Oberseite des einen Behälters (52) und zum Transport der Pipetten (62) mit aufgenommenen Reagenzien von den Behältern (52) mit offener Oberseite zu einer ausgewählten Gruppe der Röhrchen (36), wobei die Steuerung ausgebildet ist, um den Kopf (30) über andere Gruppen der Röhrchen (36) als die ausgewählte Gruppe der Röhrchen (36) zu bewegen, wobei sich die Pipetten (62) zwischen den Röhrchen (36) befinden, wenn sie sich über die anderen Gruppen von Röhrchen (36) bewegen.

2. Die Proben-Handhabungsvorrichtung gemäß Anspruch 1, worin der gleichmäßige Abstand zwischen den von dem Kopf (30) getragenen Pipetten (62) einstellbar ist und die Steuerung weiter den Kopf (30) steuert, um den Abstand zwischen den Pipetten (62) so einzustellen, dass er dem gleichmäßigen Abstand der Gestelle (34) entspricht, über welche sich die Pipetten (62) bewegen.

Revendications

1. Dispositif de manipulation de spécimen, comprenant :

un plancher (22) sur lequel est définie une pluralité de positions, comprenant une pluralité de réceptacles ouverts sur le dessus (52), chacun adapté pour contenir à l'intérieur un réactif ;

une tête (30) adaptée pour transporter des fluides sélectionnés dans X pipettes (62) sur ledit plancher (22), X valant 3 ou plus ;

un dispositif d'entraînement et de commande commandant le mouvement de ladite tête (30) pour prendre des pipettes (62) agencées en une rangée avec un espacement uniforme entre elles ;

caractérisé en ce que ledit dispositif de manipulation comprend en outre des râteliers (34) sur ledit plancher (22) pour supporter des tubes individuels ouverts sur le dessus (36) dans des groupes de X, lesdits râteliers (34) supportant lesdits tubes (36) dans chaque groupe avec ledit espacement uniforme, ledit dispositif de commande étant adapté pour commander le mouvement de ladite tête (30) pour déplacer la rangée prise de pipettes (62) vers l'un desdits réceptacles ouverts sur le dessus (52) pour prendre un réactif approprié à travers le dessus ouverts dudit réceptacle (52), pour déplacer les pipettes (62) avec les réactifs pris à partir desdits réceptacles ouverts sur le dessus (52) vers un groupe sélectionné desdits tubes (36), ledit dispositif de commande étant adapté pour déplacer ladite tête (30) sur des groupes desdits tubes (36) autres que ledit groupe sélectionné desdits tubes (36) avec lesdites pipettes (62) entre les tubes (36) lorsqu'ils passent au-dessus desdits autres groupes de tubes (36).

2. Dispositif de manipulation de spécimen selon la revendication 1, dans lequel ledit espacement uniforme entre lesdites pipettes (62) portées par ladite tête (30) est ajustable, et ledit dispositif de commande commande en outre ladite tête (30) pour ajuster ledit espacement entre lesdites pipettes (62) pour correspondre à l'espacement uniforme des râteliers (34) sur lesquels passent lesdites pipettes (62).

Drawing